Effects of anticoagulant treatment on intestinal ischaemia and reperfusion injury in rats.

BACKGROUND: In recent years it has become increasingly clear that a cross-talk between the inflammatory response and blood coagulation exists, although many of the underlying mechanisms remain unclear. In the present study we investigated the potential anti-inflammatory properties of two different anticoagulant compounds, i.e. active-site inactivated FVIIa (FVIIai) and fondaparinux sodium, a selective FXa inhibitor, administered as pretreatment in a model of intestinal I/R in rats.

METHODS: Endothelial barrier permeability was assessed using the vascular leakage of radiolabelled human serum albumin, tissue neutrophil sequestration was quantitated by myeloperoxidase (MPO) activity, and plasma levels of macrophage inflammatory protein (MIP)-2 were examined using an enzyme-linked-immuno-sorbent assay after 40 min of intestinal ischaemia and 6 h of reperfusion in the rat (n = 34). Pretreatment with FVIIai or fondaparinux sodium was administered 90 min before initiation of ischaemia.

RESULTS: Endothelial-barrier permeability in all examined organs, myeloperoxidase activity in the lungs, and ileum and MIP-2 levels in plasma increased after intestinal I/R. Pretreatment with FVIIai decreased the endothelial barrier permeability and MPO activity in the ileum, and a tendency towards decreased permeability was also observed in the lungs. Fondaparinux did not affect the endothelial barrier permeability or MPO activity. Both FVIIai and fondaparinux decreased the MIP-2 levels in plasma after intestinal I/R.

CONCLUSIONS: Inhibition of the TF-FVIIa complex by FVIIai can attenuate inflammatory responses in connection with intestinal I/R-injury and could represent a potentially important therapeutic strategy for the prevention of organ dysfunction. Potential anti-inflammatory properties of fondaparinux and other inhibitors of FXa are not excluded and need further investigation.